Despite decades of research, therapeutic discoveries, and technical innovations, the preterm birth rate continues to rise, particularly in nulliparous women. Researchers have sought to identify genes and genetic variants which are risk factors for preterm birth. However, these studies have been hampered by several limitations, including small sample size, reducing the power to detect association, as well as a heterogeneous population that was not limited to nulliparous women. Given the cost and scope of the problem of preterm birth, utilizing new genomic and proteomic technologies to dissect the etiology of preterm birth is imperative. The long-term research goal is to identify a series of DNA polymorphisms and physiologic biomarkers that will improve the understanding of the disease and will identify the subset of nulliparous women at greatest risk for early preterm birth which would allow for targeted intervention or the institution of preventive measures and strategies for this high-risk group. The objective of this application is to join a network of centers dedicated to collecting specimens and information from pregnant nulliparous women. It is expected that a large biorepository will allow for sufficient volume of specimens to test genetic and biomarker hypotheses rigorously, allowing for the discovery of a unique set of genes and biomarkers to serve as diagnostic and treatment targets. The research proposed will conduct a Genomewide association study (GWAS) for the outcome of preterm birth to identify a set of genetic variants associated with preterm birth. In addition, a gene-environment interaction analysis will be performed to control for important environmental influences known to be associated with preterm birth. This proposal is novel in that no prior GWAS has been reported for preterm birth in nulliparous women. Additionally, prior single gene association studies have not controlled for potentially confounding environmental factors in a large, well characterized sample. The research is significant in that preterm birth leads to considerable neonatal morbidity, mortality, and health care costs. It is imperative to develop new strategies to understand this and other pregnancy complications to better prevent, diagnose, and treat conditions such as preterm birth.